Parkinson's disease (PD) is a chronic and progressive motor system disorder inflicting profound social and economic costs worldwide. It is the second most common neurodegenerative disorder after Alzheimer's disease (AD), affecting more than 1% of 55-year-old individuals and more than 3% of those over the age of 75 (de Lau et al. (2006) Lancet Neurology 5:525-535). The primary symptoms of PD include tremor, rigidity, bradykinesia, and postural instability (Jankovic (2008) Journal of Neurology, Neurosurgery, and Psychiatry 79:368-376). The cardinal pathological feature of PD is the loss of dopaminergic neurons in the substantia nigra, a brain region involved in coordination and control of muscle activity (Hornykiewicz (2006) J Neural Transm Suppl 70:9-15). Although PD manifests primarily as a motor disability, recent studies reveal many pre-motor symptoms that suggest an onset of PD pathology years before characteristic symptoms appear. By the time a diagnosis is made, at least one-third of substantia nigra neurons and striatal dopaminergic fibers are already lost (Greffard et al. (2006) Arch Neurol 63:584-588).
Despite years of research, there is no one test or technique that can provide a conclusive primary diagnosis of PD. Current diagnostic methods are based on medical history evaluation and a combination of physical and neurological assessments (Hughes et al. (2002) Brain: A Journal of Neurology 125:861-870; Gelb et al. (1999) Archives of Neurology 56:33-39). Standard practices for these assessments, such as the Unified Parkinson's Disease Rating Scale (UPDRS; Goetz et al. (2008) Movement Disorders 23:2129-2170) have aided tremendously in clinical staging of the disease, but fail to detect PD before the onset of initial motor symptoms. Additional techniques, such as CT, MRI, and PET neuroimaging, may be used to rule out other neurological disorders, but rarely do they detect any abnormality that can be directly related to the onset of PD (Stoessl (2011) Neurotherapeutics 8:72-81). There are also no laboratory tests utilizing blood, cerebrospinal fluid, or urine samples that have proven to be effective in primary diagnosis or confirmation of PD.
Thus, there is a need for an accurate, relatively non-invasive, and affordable PD diagnostic test, especially one that can identify the condition at an early stage of the disease, even before significant physical symptoms are expressed. This is particularly true given widespread recognition that early detection facilitating early treatment helps to slow the progression of the disease, minimize symptoms, and improve the overall quality of life (DeKosky et al. Science 302:830-834).